Variant rs80008695 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_025074.7(FRAS1):c.2575+20A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,566,466 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 63 hom. )

Consequence

FRAS1
NM_025074.7 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.479

Variant links:

Genes affected

FRAS1 (HGNC:19185): (Fraser extracellular matrix complex subunit 1) This gene encodes an extracellular matrix protein that appears to function in the regulation of epidermal-basement membrane adhesion and organogenesis during development. Mutations in this gene cause Fraser syndrome, a multisystem malformation that can include craniofacial, urogenital and respiratory system abnormalities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

FRAS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 4-78363685-A-C is Benign according to our data. Variant chr4-78363685-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 445933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00503 (766/152296) while in subpopulation AMR AF= 0.0466 (712/15294). AF 95% confidence interval is 0.0437. There are 22 homozygotes in gnomad4. There are 459 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRAS1	NM_025074.7 linkuse as main transcript	c.2575+20A>C		intron_variant		ENST00000512123.4	NP_079350.5
FRAS1	NM_001166133.2 linkuse as main transcript	c.2575+20A>C		intron_variant			NP_001159605.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4 linkuse as main transcript	c.2575+20A>C	intron_variant	5	NM_025074.7	ENSP00000422834	P1	Q86XX4-2
FRAS1	ENST00000325942.11 linkuse as main transcript	c.2575+20A>C	intron_variant	1		ENSP00000326330		Q86XX4-5
FRAS1	ENST00000682513.1 linkuse as main transcript	c.2575+20A>C	intron_variant			ENSP00000508201
FRAS1	ENST00000684159.1 linkuse as main transcript	c.2575+20A>C	intron_variant			ENSP00000506875

Frequencies

GnomAD3 genomes

AF:

0.00504

AC:

767

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0467

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00787

AC:

1390

AN:

176542

Hom.:

AF XY:

0.00614

AC XY:

573

AN XY:

93340

show subpopulations

Gnomad AFR exome

AF:

0.000720

Gnomad AMR exome

AF:

0.0519

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000545

Gnomad OTH exome

AF:

0.00479

GnomAD4 exome

AF:

0.00139

AC:

1963

AN:

1414170

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

832

AN XY:

698798

show subpopulations

Gnomad4 AFR exome

AF:

0.000372

Gnomad4 AMR exome

AF:

0.0495

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000267

Gnomad4 OTH exome

AF:

0.00133

GnomAD4 genome

AF:

0.00503

AC:

766

AN:

152296

Hom.:

Cov.:

AF XY:

0.00616

AC XY:

459

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.0466

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.000386

Hom.:

Bravo

AF:

0.00720

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 31, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.8

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over